This project is aimed at understanding the role of enzyme systems in host immune defense, specifically the NADPH oxidase. We are interested in understanding the role of the NADPH oxidase in the generation and control of inflammation and its role in protection from infection. This work will be informative on how to manipulate the host immune system pharmacologically and immunologically. We have used a mouse created in my laboratory that is deficient in the NADPH oxidase and closely mimics NADPH oxidase deficiency in humans, chronic granulomatous disease (CGD). In addition to our work on the NADPH oxidase, we are pursuing the underlying basis of another host defense defect, hyper-IgE and recurrent infection syndrome or Jobs syndrome. Since this appears to be an autosomal dominant disease characterized by extremely elevated IgE, recurrent sino-pulmonary infections, osteopenia, kyphoscoliosis, pulmonary cysts, and dental abnormalities, identification of the gene(s) will be very important in our understanding of the host immune response as well as skeletal growth and development.